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Gold-Coated Superparamagnetic Iron Oxide Nanoparticles Attenuate Collagen-Induced Arthritis after Magnetic Targeting

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Abstract

The aim of the study was to evaluate if gold-coated superparamagnetic iron oxide nanoparticles (AuSPION) magnetic-targeted to the arthritic articulation of collagen induced arthritis (CIA) rats are able to ameliorate rheumatoid arthritis without producing significant biological adverse effects in comparison to colloidal Au nanoparticles (AuC) and metotrexate (MTX). Male Wistar rats were divided into control; arthritic; AuSPION (150 μg kg−1); AuC (150 μg kg−1) and MTX (2.5 μg kg−1). Treatments were administered thrice every other day by the intraperitoneal route 15 min after all groups had a neodymium magnet coupled to the right ankle joint (kept for 1 h). Paw edema and body weight were measured weekly. Joint sections were evaluated by Haematoxylin & Eosin and immunohistochemistry (TNF-α, IL-1β). Biomarkers of oxidative stress were used to evaluate toxicity. Among the evaluated treatments, AuSPION led to significant clinical improvements (decreased edema and infiltration by leukocytes as well as less positively immunostained cells for both TNF-α and IL-1β in synovium) accompanied by a lack of toxicity as indicated by redox state and genotoxicity assays. Our results clearly indicate that the magnetic targeting of AuSPION suppresses joint edema and inflammation, cytokine expression as well as the redox imbalance, thereby contributing to an amelioration of arthritis severity in CIA rats. The results demonstrate for the first time the potentiality of AuSPION administration under a magnetic field as an attractive alternative for future treatments of rheumatic diseases.

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Acknowledgements

The authors acknowledge the staff of Laboratório de Histologia da Faculdade de Odontologia de Ribeirão Preto (FORP/USP), Laboratório de Farmacologia do Instituto Butantan and Laboratório de Neuroendocrinologia da Faculdade de Medicina de Ribeirão Preto (USP) and to Ana Flavia do Bem Afonso for technical support. Authors are grateful to Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP) for financial support (FAPESP 2014/06744-4 and FAPESP 2015/0538-0).

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Correspondence to Maria Fernanda Hornos Carneiro.

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The authors declare no competing financial or non-financial interests. The results of this study were obtained in compliance with the NC3Rs ARRIVE guidelines [73]. Procedures were developed also in accordance with the guidelines of the Committee on the Care and Use of Experimental Animal Resources of the University of Sao Paulo after the approval of the study by the same Committee (opinion number: 14.1.550.53.7).

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Carneiro, M.H., Machado, A.R.T., Antunes, L.M.G. et al. Gold-Coated Superparamagnetic Iron Oxide Nanoparticles Attenuate Collagen-Induced Arthritis after Magnetic Targeting. Biol Trace Elem Res 194, 502–513 (2020). https://doi.org/10.1007/s12011-019-01799-z

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Key-Words

  • Gold nanoparticles
  • Iron oxide nanoparticles
  • Inflammation
  • Magnetism
  • Toxicity
  • Collagen-induced arthritis